Axially Chiral 2-Arylimino-3-aryl-thiazolidine-4-one Derivatives:  Enantiomeric Separation and Determination of Racemization Barriers by Chiral HPLC

Abstract

Axially chiral 2-arylimino-3-aryl-thiazolidine-4-ones have been synthesized as racemic mixtures, and each mixture with the exception of 2-(o-chlorophenyl)imino-3-(o-chlorophenyl)-thiazolidine-4-one has been converted to the corresponding 5-benzylidene-2-arylimino-3-aryl-thiazolidine-4-one racemates by reaction with benzaldehyde. The thermally interconvertible enantiomers of each compound have been obtained by enantioselective HPLC separation on columns Chiralpak AD-H and Chiralcel OD-H, and the barriers to racemization have been found to be 98.1-114.1 kJ/mol. The barriers determined were compared to those of structurally related compounds to provide evidence for the stereochemistry of the aryl imino bond.

Inhibitors of HCV NS5A: From Iminothiazolidinones to Symmetrical Stilbenes

“…6,7 This compound had been prepared as part of a prospective library according to the synthetic route depicted in Scheme 1, where regiocontrol during ring closure occurred as anticipated based on literature precedent. [8][9][10] Assignment of the 2-arylimino Z-configuration is also based on prior studies, a function of minimizing unfavorable steric interactions, 11,12 while the C-5 position is configurationally unstable and cannot be defined. 13 Screening results for additional library members were available (see compounds 3-7) and gave indication that antiviral activity was closely associated with the embedded amino acid moiety (Table 1).…”

Facile Synthesis and Quantitative Structure–Activity Relationship Study of Antitumor Active 2-(4-Oxo-thiazolidin-2-ylidene)-3-oxo-propionitriles

“…The appearance of the ylidene proton of compounds 4a-c, 4f-h at δ= 7.78-7.86 confirmed the formation of Z-isomers. 9,15,[23][24][25][26][27][28] On the other hand, the ylidene proton of compounds 4d and 4i were revealed at δ= 8.00-8.16, slightly downfield shifted than the other synthesized analogues, which could be attributed to the anisotropic effect of the hydroxyl group oriented at the o-position of the arylidene function. Furthermore, reaction of 4-thiazolidinones 3a, b with formaldehyde and the appropriate heteroalicyclic amines (pyrrolidine, piperidine, morpholine and N-methylpiperazine) through Mannich reaction yielded 5a-h.…”

Axially chiral N-(o-aryl)-2-thioxo-oxazolidine-4-one and rhodanine derivatives: enantiomeric separation and determination of racemization barriers

“…12 The barrier for this compound in this work was found to be 119.5 kJ/mol when the racemization was carried out in ethanol at 348 K. The difference appears more likely to be a temperature effect, rather than a solvent effect, when the activation barrier of the structurally similar N-(o-tolyl)rhodanine determined at different temperatures and solvents is compared. For this compound, an activation barrier of 109.3 kJ/mol was found 19 …”

“…After the enantiomers of (±)-2-12 were resolved by chiral chromatography, thermal racemizations were performed on the single enantiomers, as has been described before, 19 (Fig. 2) in order to determine the activation energy barriers to racemization ( Table 4).…”

“…Based on our experiences with thermally interconvertible, axially chiral compounds, [11][12][13][14][15][16][17][18][19] the synthesis of N-ortho-aryl-substituted heterocyclic compounds, as shown in Scheme 1, has been planned.…”